On the occurrence of cytochrome P450 in viruses

Abstract

Genes encoding cytochrome P450 (CYP; P450) enzymes occur widely in the Archaea, Bacteria, and Eukarya, where they play important roles in metabolism of endogenous regulatory molecules and exogenous chemicals. We now report that genes for multiple and unique P450s occur commonly in giant viruses in the Mimiviridae, Pandoraviridae, and other families in the proposed order Megavirales. P450 genes were also identified in a herpesvirus (Ranid herpesvirus 3) and a phage (Mycobacterium phage Adler). The Adler phage P450 was classified as CYP102L1, and the crystal structure of the open form was solved at 2.5 Å. Genes encoding known redox partners for P450s (cytochrome P450 reductase, ferredoxin and ferredoxin reductase, and flavodoxin and flavodoxin reductase) were not found in any viral genome so far described, implying that host redox partners may drive viral P450 activities. Giant virus P450 proteins share no more than 25% identity with the P450 gene products we identified in Acanthamoeba castellanii, an amoeba host for many giant viruses. Thus, the origin of the unique P450 genes in giant viruses remains unknown. If giant virus P450 genes were acquired from a host, we suggest it could have been from an as yet unknown and possibly ancient host. These studies expand the horizon in the evolution and diversity of the enormously important P450 superfamily. Determining the origin and function of P450s in giant viruses may help to discern the origin of the giant viruses themselves.

Tricarboxylic acid cycle and proton gradient inPandoravirus massiliensis: Is it still a virus?

“…genes, encoding enzymes that are known to be essential in the metabolism of endogenous regulatory molecules and exogenous drugs, but not their ancillary enzymatic redox partners, which could be recruited from host (12). Recently, a deep analysis of 501 environmental metagenome-assembled genomes of NCLDV revealed a diversity of metabolic genes involved in nutrient uptake, light harvesting, nitrogen metabolism, glycolysis and the TCA cycle (41).…”

“…Subsequently, an almost complete protein translation apparatus was discovered in Tupanvirus and Klosneuviruses (9,10). More recently, it was found that genes encoding multiple and unique cytochromes P450 monooxygenases commonly occur in giant viruses in the Mimiviridae, Pandoraviridae, and other families in the proposed order Megavirales (11,12).…”

Giant virus vs amoeba: fight for supremacy

“…Sequences of several giant viruses were found in human microbiome, but nothing is known about their interaction profile and ecological roles [94, 95]. Furthermore, it has been found that these viruses can encode genes that act on complex biochemical pathways [96–98]. The wide distribution and diversity of giant viruses associated with their powerful gene arsenal, both known and unknown, can reflect the wide range of interaction strategies.…”

More P450s Are Involved in Secondary Metabolite Biosynthesis in Streptomyces Compared to Bacillus, Cyanobacteria, and Mycobacterium

“…Because of the presence of this prosthetic group, these enzymes absorb wavelengths at 450 nm; thus, the name P450s has been assigned to these proteins [ 3 , 4 , 5 , 6 ]. Since their identification, a large number of P450s have been identified in almost all living organisms [ 7 ] and, surprisingly, in non-living entities as well [ 8 ]. The regio- and stereo-specific catalytic nature of these enzymes makes them essential for the survival of some organisms, and these enzymes are thus good drug targets in the case of pathogenic organisms [ 9 , 10 , 11 , 12 , 13 ].…”